The construction of a portacaval shunt, causing complete diversion of portal blood from the liver has been shown in this laboratory to alter significantly the establishment and growth of different types of tumors in rats. Dimethylbenz (a) anthracene (DMBA)-induced mammary tumors are greatly inhibited in rats with a shunt. Likewise, intrahepatic growth of ovarian tumors or the virulent Novikoff hepatoma (intrahepatic) are considerably inhibited in rats with a portacaval shunt. On the other hand, the growth of a strain of Morris hepatoma (with a medium rate of growth) is significantly increased when implanted in the groin of rats with portacaval shunt. Thus, the presence of a portacaval shunt can either promote or inhibit the establishment and growth of tumors, depending on the type of tumor and its location. It has also been found that the extracts of shunted liver when administered to rats greatly promotes the establishment and growth of DMBA- induced mammary tumors, as compared with rats receiving "sham" liver plus DMBA or DMBA alone. Recent collaborative in vitro experiments have indicated that the extracts of liver, especially shunted liver, have a wide range of interesting biological activities when incubated with different types of cell cultures. The objective of this project is to investigate the possible mechanisms of modification of tumor growth by portacaval shunt. Particularly we propose to follow two approaches to this problem. The first approach is to investigate the effect of construction of portacaval shunt on tumors of different types and tumors in different locations. The second objective is to investigate the possible influence of extracts of rat liver, especially liver from a rat with a portacaval shunt on the growth of tumor both in vivo and in vitro.